• 2965 Citations
  • 23 h-Index
20022018
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Research Output 2002 2018

  • 2965 Citations
  • 23 h-Index
  • 48 Article
  • 1 Conference contribution
  • 1 Review article
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Article
2018

Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis

Haque, A. K. M. A., Dewerth, A., Antony, J. S., Riethmüller, J., Schweizer, G. R., Weinmann, P., Latifi, N., Yasar, H., Pedemonte, N., Sondo, E., Weidensee, B., Ralhan, A., Laval, J., Schlegel, P., Seitz, C., Loretz, B., Lehr, C-M., Handgretinger, R. & Kormann, M. S. D., Nov 13 2018, In : Scientific Reports. 8, 1, p. 16776

Research output: Contribution to journalArticle

Cystic Fibrosis
Nanoparticles
Lung
Messenger RNA
Viral DNA
7 Citations (Scopus)

High-throughput screening identifies FAU protein as a regulator of mutant cystic fibrosis transmembrane conductance regulator channel

Tomati, V., Pesce, E., Caci, E., Sondo, E., Scudieri, P., Marini, M., Amato, F., Castaldo, G., Ravazzolo, R., Galietta, L. J. V. & Pedemonte, N., Jan 1 2018, In : Journal of Biological Chemistry. 293, 4, p. 1203-1217 15 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Screening
Throughput
Proteins
Cell membranes

Pharmacological Inhibition of the Ubiquitin Ligase RNF5 Rescues F508del-CFTR in Cystic Fibrosis Airway Epithelia

Sondo, E., Falchi, F., Caci, E., Ferrera, L., Giacomini, E., Pesce, E., Tomati, V., Mandrup Bertozzi, S., Goldoni, L., Armirotti, A., Ravazzolo, R., Cavalli, A. & Pedemonte, N., Jul 19 2018, In : Cell Chemical Biology. 25, 7, p. 891-905.e8

Research output: Contribution to journalArticle

Ligases
Ubiquitin
Cystic Fibrosis
Epithelium
Pharmacology
9 Citations (Scopus)

Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools

Liessi, N., Cichero, E., Pesce, E., Arkel, M., Salis, A., Tomati, V., Paccagnella, M., Damonte, G., Tasso, B., Galietta, L. J. V., Pedemonte, N., Fossa, P. & Millo, E., Jan 20 2018, In : European Journal of Medicinal Chemistry. 144, p. 179-200 22 p.

Research output: Contribution to journalArticle

Thiazoles
Quantitative Structure-Activity Relationship
Derivatives
Cystic Fibrosis Transmembrane Conductance Regulator
Molecules

The Autophagy Inhibitor Spautin-1 Antagonizes Rescue of Mutant CFTR Through an Autophagy-Independent and USP13-Mediated Mechanism

Pesce, E., Sondo, E., Ferrera, L., Tomati, V., Caci, E., Scudieri, P., Musante, I., Renda, M., Baatallah, N., Servel, N., Hinzpeter, A., di Bernardo, D., Pedemonte, N. & Galietta, L. J. V., 2018, In : Frontiers in Pharmacology. 9, p. 1464

Research output: Contribution to journalArticle

Autophagy
Cystic Fibrosis
Biological Phenomena
Chloride Channels
Quality Control

Therapeutic approaches to CFTR dysfunction: From discovery to drug development

Li, H., Pesce, E., Sheppard, D. N., Singh, A. K. & Pedemonte, N., 2018, In : Journal of Cystic Fibrosis. 17, 2, p. S14-S21

Research output: Contribution to journalArticle

2017

In vitro recapitulation of the site-specific editing (to wild-type) of mutant IDS mRNA transcripts, and the characterization of IDS protein translated from the edited mRNAs

Lualdi, S., Del Zotto, G., Zegarra-Moran, O., Pedemonte, N., Corsolini, F., Bruschi, M., Tomati, V., Amico, G., Candiano, G., Dardis, A., Cooper, D. N. & Filocamo, M., Jul 2017, In : Human Mutation. 38, 7, p. 849-862 14 p.

Research output: Contribution to journalArticle

Iduronate Sulfatase
Messenger RNA
Proteins
Uridine
Mucopolysaccharidosis II
2016
3 Citations (Scopus)

Phenylhydrazones as Correctors of a Mutant Cystic Fibrosis Transmembrane Conductance Regulator

Nieddu, E., Pollarolo, B., Mazzei, M. T., Anzaldi, M., Schenone, S., Pedemonte, N., Galietta, L. J. V. & Mazzei, M., Feb 1 2016, In : Archiv der Pharmazie. 349, 2, p. 112-123 12 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Furaldehyde
Thiophenes
Epithelial Cells
2015
2 Citations (Scopus)

Development of the olfactory epithelium and Nasal Glands in TMEM16A-/-and TMEM16A+/ +Mice

Maurya, D. K., Henriques, T., Marini, M., Pedemonte, N., Galietta, L. J. V., Rock, J. R., Harfe, B. D. & Menini, A. M., Jun 11 2015, In : PLoS One. 10, 6, e0129171.

Research output: Contribution to journalArticle

Olfactory Mucosa
Ablation
Nose
Neurons
Olfactory Marker Protein
18 Citations (Scopus)

Genetic Inhibition of the Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated to F508del Cystic Fibrosis Mutation

Tomati, V., Sondo, E., Armirotti, A., Caci, E., Pesce, E., Marini, M., Gianotti, A., Ju Jeon, Y., Cilli, M., Pistorio, A., Mastracci, L., Ravazzolo, R., Scholte, B., Ronai, Z., Galietta, L. J. V. & Pedemonte, N., Jul 17 2015, In : Scientific Reports. 5, 12138.

Research output: Contribution to journalArticle

Ligases
Ubiquitin
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Phenotype
8 Citations (Scopus)
Cystic Fibrosis Transmembrane Conductance Regulator
Pyrimidines
Cystic Fibrosis
Pharmacology
Mutation
13 Citations (Scopus)

Synthesis and structure-activity relationship of aminoarylthiazole derivatives as correctors of the chloride transport defect in cystic fibrosis

Pesce, E., Bellotti, M., Liessi, N., Guariento, S., Damonte, G., Cichero, E., Galatini, A., Salis, A., Gianotti, A., Pedemonte, N., Zegarra-Moran, O., Fossa, P., Galietta, L. J. V. & Millo, E., Jun 1 2015, In : European Journal of Medicinal Chemistry. 99, p. 14-35 22 p., 7909.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Structure-Activity Relationship
Cystic Fibrosis
Chlorides
Derivatives
2014
195 Citations (Scopus)

Structure and function of tmem16 proteins (anoctamins)

Pedemonte, N. & Galietta, L. J. V., 2014, In : Physiological Reviews. 94, 2, p. 419-459 41 p.

Research output: Contribution to journalArticle

Ion Transport
Ion Channels
Phospholipid Transfer Proteins
Light Signal Transduction
Lipids
3 Citations (Scopus)

The search for a common structural moiety among selected pharmacological correctors of the mutant CFTR chloride channel

Nieddu, E., Pollarolo, B., Mazzei, M. T., Anzaldi, M., Schenone, S., Pedemonte, N., Pesce, E., Galietta, L. J. V. & Mazzei, M., Nov 1 2014, In : Future Medicinal Chemistry. 6, 17, p. 1857-1868 12 p.

Research output: Contribution to journalArticle

Pyrazines
Chloride Channels
Cystic Fibrosis
Endoplasmic Reticulum
Cell Membrane
2013
20 Citations (Scopus)

In Type 1 Diabetes a Subset of Anti-Coxsackievirus B4 Antibodies Recognize Autoantigens and Induce Apoptosis of Pancreatic Beta Cells

Bason, C., Lorini, R., Lunardi, C., Dolcino, M., Giannattasio, A., d'Annunzio, G., Rigo, A., Pedemonte, N., Corrocher, R. & Puccetti, A., Feb 28 2013, In : PLoS One. 8, 2, e57729.

Research output: Contribution to journalArticle

autoantigens
Enterovirus
insulin-dependent diabetes mellitus
islets of Langerhans
Autoantigens
2012
72 Citations (Scopus)

Association of TMEM16A chloride channel overexpression with airway goblet cell metaplasia

Scudieri, P., Caci, E., Bruno, S., Ferrera, L., Schiavon, M., Sondo, E., Tomati, V., Gianotti, A., Zegarra-Moran, O., Pedemonte, N., Rea, F., Ravazzolo, R. & Galietta, L. J. V., Dec 2012, In : Journal of Physiology. 590, 23, p. 6141-6155 15 p.

Research output: Contribution to journalArticle

Chloride Channels
Goblet Cells
Metaplasia
Interleukin-4
Epithelial Cells
2 Citations (Scopus)

Asymmetric 4-Aryl-1,4-dihydropyridines Potentiate Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

Giampieri, M., Vanthuyne, N., Nieddu, E., Mazzei, M. T., Anzaldi, M., Pedemonte, N., Galietta, L. J. V., Roussel, C. & Mazzei, M., Oct 2012, In : ChemMedChem. 7, 10, p. 1799-1807 9 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Enantiomers
Ion Channels
Cystic Fibrosis
Assays
6 Citations (Scopus)

Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

Visentin, S., Ermondi, G., Medana, C., Pedemonte, N., Galietta, L. & Caron, G., Sep 2012, In : European Journal of Medicinal Chemistry. 55, p. 188-194 7 p.

Research output: Contribution to journalArticle

Chloride Channels
Cystic Fibrosis
Computer Simulation
Solubility
Ligands
15 Citations (Scopus)

Pharmacological correctors of mutant CFTR mistrafficking

Pedemonte, N. & Galietta, L. J. V., 2012, In : Frontiers in Pharmacology. 3 OCT, Article 175.

Research output: Contribution to journalArticle

Pharmacology
Cystic Fibrosis
Mutation
Proteins
Small Molecule Libraries
2011
45 Citations (Scopus)

Cystic fibrosis: A new target for 4-imidazo[2,1-b]thiazole-1, 4-dihydropyridines

Budriesi, R., Ioan, P., Leoni, A., Pedemonte, N., Locatelli, A., Micucci, M., Chiarini, A. & Galietta, L. J. V., Jun 9 2011, In : Journal of Medicinal Chemistry. 54, 11, p. 3885-3894 10 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Felodipine
Inborn Genetic Diseases
Chloride Channels
43 Citations (Scopus)

Dual activity of aminoarylthiazoles on the trafficking and gating defects of the cystic fibrosis transmembrane conductance regulator chloride channel caused by cystic fibrosis mutations

Pedemonte, N., Tomati, V., Sondo, E., Caci, E., Millo, E., Armirotti, A., Damonte, G., Zegarra-Moran, O. & Galietta, L. J. V., Apr 29 2011, In : Journal of Biological Chemistry. 286, 17, p. 15215-15226 12 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Cystic Fibrosis
Defects
Mutation
17 Citations (Scopus)

High-throughput screening of libraries of compounds to identify CFTR modulators.

Pedemonte, N., Zegarra-Moran, O. & Galietta, L. J. V., 2011, In : Methods in molecular biology (Clifton, N.J.). 741, p. 13-21 9 p.

Research output: Contribution to journalArticle

Chloride Channels
Iodides
Cystic Fibrosis
Libraries
Diarrhea
30 Citations (Scopus)
ciclopirox
Aminacrine
Chloride Channels
Gene Expression Profiling
Epithelial Cells
2010
75 Citations (Scopus)
Pharmacology
Cystic Fibrosis
Mutation
Isoxazoles
Cystic Fibrosis Transmembrane Conductance Regulator
66 Citations (Scopus)

Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

Kalid, O., Mense, M., Fischman, S., Shitrit, A., Bihler, H., Ben-Zeev, E., Schutz, N., Pedemonte, N., Thomas, P. J., Bridges, R. J., Wetmore, D. R., Marantz, Y. & Senderowitz, H., Dec 2010, In : Journal of Computer-Aided Molecular Design. 24, 12, p. 971-991 21 p.

Research output: Contribution to journalArticle

Computer Simulation
Screening
screening
Nucleotides
Binding Sites
2009
31 Citations (Scopus)

Epithelial sodium channel inhibition in primary human bronchial epithelia by transfected siRNA

Caci, E., Melani, R., Pedemonte, N., Yueksekdag, G., Ravazzolo, R., Rosenecker, J., Galietta, L. J. V. & Zegarra-Moran, O., Feb 1 2009, In : American Journal of Respiratory Cell and Molecular Biology. 40, 2, p. 211-216 6 p.

Research output: Contribution to journalArticle

Epithelial Sodium Channels
Small Interfering RNA
Epithelium
Cystic Fibrosis Transmembrane Conductance Regulator
Fluids
18 Citations (Scopus)

Mutation-specific potency and efficacy of cystic fibrosis transmembrane conductance regulator chloride channel potentiators

Caputo, A., Hinzpeter, A., Caci, E., Pedemonte, N., Arous, N., Di Duca, M., Zegarra-Moran, O., Fanen, P. & Galietta, L. J. V., 2009, In : Journal of Pharmacology and Experimental Therapeutics. 330, 3, p. 786-791 6 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Mutation
Felodipine
Cystic Fibrosis
21 Citations (Scopus)

Synthesis of 4-thiophen-2′-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel

Cateni, F., Zacchigna, M., Pedemonte, N., Galietta, L. J. V., Mazzei, M. T., Fossa, P., Giampieri, M. & Mazzei, M., Dec 1 2009, In : Bioorganic and Medicinal Chemistry. 17, 23, p. 7894-7903 10 p.

Research output: Contribution to journalArticle

Bearings (structural)
Chloride Channels
Genistein
Cystic Fibrosis
Assays
2008
792 Citations (Scopus)

TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity

Caputo, A., Caci, E., Ferrera, L., Pedemonte, N., Barsanti, C., Sondo, E., Pfeffer, U., Ravazzolo, R., Zegarra-Moran, O. & Galietta, L. J. V., Oct 24 2008, In : Science. 322, 5901, p. 590-594 5 p.

Research output: Contribution to journalArticle

Calcium Chloride
Chloride Channels
Membrane Proteins
Interleukin-4
Olfactory Perception
2007
9 Citations (Scopus)

Block of CFTR-dependent chloride currents by inhibitors of multidrug resistance-associated proteins

Diena, T., Melani, R., Caci, E., Pedemonte, N., Sondo, E., Zegarra-Moran, O. & Galietta, L. J. V., Apr 10 2007, In : European Journal of Pharmacology. 560, 2-3, p. 127-131 5 p.

Research output: Contribution to journalArticle

Multidrug Resistance-Associated Proteins
Cystic Fibrosis Transmembrane Conductance Regulator
Chlorides
Membrane Proteins
Benzbromarone
39 Citations (Scopus)

Proteomic analysis of the airway surface liquid: Modulation by proinflammatory cytokines

Candiano, G., Bruschi, M., Pedemonte, N., Musante, L., Ravazzolo, R., Liberatori, S., Bini, L., Galietta, L. J. V. & Zegarra-Moran, O., Jan 2007, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 292, 1

Research output: Contribution to journalArticle

Proteomics
Cytokines
Proteins
Epithelium
Mucociliary Clearance
31 Citations (Scopus)

Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions

Fujii, N., Haresco, J. J., Novak, K. A. P., Gage, R. M., Pedemonte, N., Stokoe, D., Kuntz, I. D. & Kiplin Guy, R., Jan 15 2007, In : Bioorganic and Medicinal Chemistry Letters. 17, 2, p. 549-552 4 p.

Research output: Contribution to journalArticle

PDZ Domains
Scaffolds
Ligands
Molecules
indole
27 Citations (Scopus)

Structure-activity relationship of 1,4-dihydropyridines as potentiators of the cystic fibrosis transmembrane conductance regulator chloride channel

Pedemonte, N., Boido, D., Moran, O., Giampieri, M., Mazzei, M., Ravazzolo, R. & Galietta, L. J. V., Jul 2007, In : Molecular Pharmacology. 72, 1, p. 197-207 11 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Structure-Activity Relationship
Mutation
Felodipine
101 Citations (Scopus)

Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: Role of pendrin and anion channels

Pedemonte, N., Caci, E., Sondo, E., Caputo, A., Rhoden, K., Pfeffer, U., Di Candia, M., Bandettini, R., Ravazzolo, R., Zegarra-Moran, O. & Galietta, L. J. V., Apr 15 2007, In : Journal of Immunology. 178, 8, p. 5144-5153 10 p.

Research output: Contribution to journalArticle

Lactoperoxidase
Oxidants
Interleukin-4
Anions
Epithelium
2006
125 Citations (Scopus)

Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells

Fang, X., Song, Y., Hirsch, J., Galietta, L. J. V., Pedemonte, N., Zemans, R. L., Dolganov, G., Verkman, A. S. & Matthay, M. A., Feb 2006, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 290, 2

Research output: Contribution to journalArticle

Alveolar Epithelial Cells
Lung
Epithelial Cells
Air
Chloride Channels

Small-molecule modulators of CFTR function discovered by high-throughput screening

Verkman, A. S., Sonawane, N. D., Lukacs, G. L., Muanprasat, C., Pedemonte, N. & Galietta, L. J. V., 2006, In : Acta Biomedica. 77, SUPPL. 3, p. 40 1 p.

Research output: Contribution to journalArticle

2005
23 Citations (Scopus)

4-Chlorobenzo[F]isoquinoline (CBIQ), a novel activator of CFTR and ΔF508 CFTR

Murthy, M., Pedemonte, N., MacVinish, L., Galietta, L. & Cuthbert, A., Jun 1 2005, In : European Journal of Pharmacology. 516, 2, p. 118-124 7 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Ion Channels
Chlorides
Epithelium
49 Citations (Scopus)
Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Antihypertensive Agents
Mutation
Isradipine
37 Citations (Scopus)

Gelsolin secretion in interleukin-4-treated bronchial epithelia and in asthmatic airways

Candiano, G., Bruschi, M., Pedemonte, N., Caci, E., Liberatori, S., Bini, L., Pellegrini, C., Viganò, M., O'Connor, B. J., Lee, T. H., Galietta, L. J. V. & Zegarra-Moran, O., Nov 1 2005, In : American Journal of Respiratory and Critical Care Medicine. 172, 9, p. 1090-1096 7 p.

Research output: Contribution to journalArticle

Gelsolin
Interleukin-4
Epithelium
Asthma
Epithelial Cells
120 Citations (Scopus)

Phenylglycine and sulfonamide correctors of defective ΔF508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating

Pedemonte, N., Sonawane, N. D., Taddei, A., Hu, J., Zegarra-Moran, O., Suen, Y. F., Robins, L. I., Dicus, C. W., Willenbring, D., Nantz, M. H., Kurth, M. J., Galietta, L. J. V. & Verkman, A. S., May 2005, In : Molecular Pharmacology. 67, 5, p. 1797-1807 11 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Sulfonamides
Colforsin
Cystic Fibrosis
414 Citations (Scopus)

Small-molecule correctors of defective ΔF508-CFTR cellular processing identified by high-throughput screening

Pedemonte, N., Lukacs, G. L., Du, K., Caci, E., Zegarra-Moran, O., Galietta, L. J. V. & Verkman, A. S., Sep 2005, In : Journal of Clinical Investigation. 115, 9, p. 2564-2571 8 p.

Research output: Contribution to journalArticle

Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Mutation
Chloride Channels
Temperature
2004
27 Citations (Scopus)

CFTR involvement in nasal potential differences in mice and pigs studied using a thiazolidinone CFTR inhibitor

Salinas, D. B., Pedemonte, N., Muanprasat, C., Finkbeiner, W. F., Nielson, D. W. & Verkman, A. S., Nov 2004, In : American Journal of Physiology - Lung Cellular and Molecular Physiology. 287, 5 31-5

Research output: Contribution to journalArticle

Nose
Swine
Colforsin
Amiloride
Cystic Fibrosis
20 Citations (Scopus)

Effect of inflammatory stimuli on airway ion transport.

Galietta, L. J. V., Folli, C., Caci, E., Pedemonte, N., Taddei, A., Ravazzolo, R. & Zegarra-Moran, O., 2004, In : Proc Am Thorac Soc. 1, 1, p. 62-65 4 p.

Research output: Contribution to journalArticle

Ion Transport
Interleukin-4
Epithelial Sodium Channels
Mucociliary Clearance
Fluids and Secretions
95 Citations (Scopus)

Evidence against the rescue of defective ΔF508-CFTR cellular processing by curcumin in cell culture and mouse models

Seng, Y., Sonawane, N. D., Salinas, D., Qian, L., Pedemonte, N., Galietta, L. J. V. & Verkman, A. S., Sep 24 2004, In : Journal of Biological Chemistry. 279, 39, p. 40629-40633 5 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Curcumin
Cell culture
Cell Culture Techniques
Processing
2003
172 Citations (Scopus)

Nanomolar affinity small molecule correctors of defective ΔF508-CFTR chloride channel gating

Yang, H., Shelat, A. A., Guy, R. K., Gopinath, V. S., Ma, T., Du, K., Lukacs, G. L., Taddei, A., Folli, C., Pedemonte, N., Galietta, L. J. V. & Verkman, A. S., Sep 12 2003, In : Journal of Biological Chemistry. 278, 37, p. 35079-35085 7 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Chloride Channels
Molecules
Cystic Fibrosis
Cell membranes
2002
153 Citations (Scopus)

High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening

Tonghui, M., Vetrivel, L., Yang, H., Pedemonte, N., Zegarra-Moran, O., Galietta, L. J. V. & Verkman, A. S., Oct 4 2002, In : Journal of Biological Chemistry. 277, 40, p. 37235-37241 7 p.

Research output: Contribution to journalArticle

Cystic Fibrosis Transmembrane Conductance Regulator
Chlorides
Screening
Throughput
Cystic Fibrosis
2 Citations (Scopus)

Spatial organization of displaced ganglion cells in the chick retina

Deplano, S. & Pedemonte, N., Nov 2002, In : Visual Neuroscience. 19, 6, p. 727-734 8 p.

Research output: Contribution to journalArticle

Ganglia
Retina
Neurons
Parturition
Neuronal Plasticity